HOW GENETIC ENGINEERING OF HUMAN EMBRYOS (AND GERMLINE EDITING) WORKS
Genetic engineering (also known as genetic editing, gene editing, or DNA editing) is theoretically possible for any living organism.
Genetic engineering is a procedure that strategically changes the genes in an organism’s DNA.
<See definitions of DNA, gene, genome, RNA, and mitochondria at bottom of this page.>
The description of genetic engineering on this page refers only to genetic engineering of human embryos in a laboratory, not to genetic therapies on adults or born children.
Scientists hope to develop therapies that will remove unwanted genetic characteristics, or add or enhance desired characteristics, for the lifetime of an unborn person. In most research publicly reported so far, the characteristics targeted are diseases, abnormalities, or disabilities.
Some researchers and companies will be more interested in highly profitable opportunities to increase capabilities like intelligence and strength, design characteristics like eye color and gender, and extend lifespan. Simple cosmetic therapies are certainly possible based on current knowledge, but enhancing capabilities like intelligence or character traits like empathy will be very complex. On the other hand, recent revelations about secret experiments have demonstrated how quickly researchers might stumble unexpectedly upon therapies that can enhance abilities like memory and efficient brain function.
Researchers in human genetic engineering experiment on the DNA of animals, unborn human embryos (multi-cell human beings up to the eighth week after conception), and more recently on human adults (called somatic cell genetic engineering).
Targeted gene engineering has been performed for several years through tools called TALENs and ZFNs. A new tool for genetic engineering called CRISPR-Cas9 (an improved version of CRISPR that uses a particular enzyme) has only recently been used by researchers. This tool is much more accurate in identifying and engineering the targeted genes. It is also much faster, so genetic engineering therapies can be researched and put into practice within a short time, even in genetic engineering of human embryos. The fairly low cost of CRISPR-Cas9 (about $75) enables scientists across the world to jump into research without the usual limits on funding from institutions and governments.
CRISPR works by deliberately adding a segment of DNA that is known to cause a genetic disorder to a bacteria. The bacteria is engaged with the human DNA, and through its natural tendency to seek out the bad gene in the human DNA, it will find it and “assassinate” it. The bacterial cells will then try to repair the DNA by putting a more desirable gene in its place.
Role of IVF
The therapies being developed for genetic engineering of human embryos involve conceiving human beings through IVF (in vitro fertilization). Scientists create multiple human embryos by combining a woman’s eggs and man’s sperm in a laboratory dish, and a favored embryo is selected to avoid “defects” or sometimes to choose characteristics like eye color and gender. Unwanted embryos are destroyed, used in research, or frozen for possible future use. The selected embryo’s DNA will be edited. Then the edited embryo will be placed in a woman’s uterus so it can grow and be born.
Genome editing or germline editing is the intentional change of inherited DNA through later generations. Genetic engineering is first performed on a single individual, and then it is hoped that the desired change in the individual will be passed to descendants so that it alters humanity permanently.
Germline editing is extremely difficult, because there is no guarantee that the hoped-for change will survive future mutations (unpredictable changes in DNA due to “mistakes” in copying new DNA or the effects of certain chemicals) or environmentally induced changes in DNA. The effects of editing genes can be highly unpredictable because there is no way to know if there are additional influences of genes and interaction of genes that may not have been known when the genetic engineering takes place.
Genetic engineering of human embryos is still a mystery and will produce dangerous, unintended effects.
It is important to note that the content of this website focuses on genetic engineering of human embryos, not of born children or adults. The kind of genetic engineering performed on embryos, which is soon after their creation, is likely to have more fundamental effects on the developing person, and there is more of a chance that genetic mutations, damage to DNA, or environmental factors can cause unpredicted effects during the person’s lifetime. Genetic engineering of embryos is also known as “germline” editing (or “genome” editing) because the changes made in DNA can be inherited by future generations.
Genetic engineering always involves risk. This is not the risk of a medical procedure, which has an immediate effect, but of the future development and health of the person (and of future generations).
In considering the risks of genetic engineering, we need to consider several questions (aside from the moral, psychological, and relationship issues that are even more important):
- Can we predict the effects of genetic engineering on the person and on future generations well enough to justify trying to “fix” genetic abnormalities or enhance certain features and capabilities?
- Do the current technologies for genetic engineering actually make the changes in DNA that are desired, with extremely high accuracy?
- Since there will always be unpredictability and risk, just how much risk is acceptable? Who decides? Who protects the interests of the individual or future generations affected?
- Can we trust the researchers, scientists, and clinics to conduct the genetic engineering so that they avoid the risks that society has deemed unacceptable? Who will regulate this? Can it be effectively regulated? Is it worth the risk?
Here are some of the reasons why predicting the unintended effects of genetic engineering of human embryos and of germline editing is enormously complex, and why certainty is impossible:
- It is rare to find a single gene that always has a specific effect on an organism. Most characteristics or abilities that we can identify in organisms are “caused” by a number of genes.
- The effect of genes often depends on how they interact. Even a basic human characteristic like height is influenced by tens of thousands of genetic variations.
- Genes influence multiple characteristics.
- It is never possible to know if a gene or combination of genes might have effects that were previously unknown.
- The “expression” (active influence) of a gene can be turned on or off, or changed, by the nature of the entire DNA sequence.
- It is only recently that scientists realized what 99% of genes do. Previously, scientists thought that these “noncoding” or “junk DNA”, which means they do not instruct the body in the making of proteins, had no purpose. Now they realize that this kind of DNA is actually involved in turning the protein-coding genes “on” or “off”. The research on these genes is just getting underway.
- The influence of a single gene on the organism can change depending on the way it interacts with other genes, proteins, and bacteria.
- Genes can mutate, which is when random “mistakes”, damage, or interaction with other substances interfere with the process of duplicating DNA in cells. The new DNA is not an exact copy of the original DNA. In order to know whether a gene will have the expected influence, scientists need to know for sure whether the gene has or has not mutated.
- The possibilities for gene mutations are unlimited and unpredictable, and scientists do not know what effect most mutations will have on the body.
- An individual’s genetic information in DNA can actually change during lifetime through their environment and experiences. These changes may be inherited by children. The rapidly changing field of science that studies these lifetime changes in DNA is called epigenetics.
- While most DNA is found in the nucleus of a cell, there is also some DNA in other structures in the cells called mitochondria. Some inherited changes in mitochondrial DNA can cause major problems for the health of a person in their organs and tissues like the heart, brain, kidneys, and muscles, with negative effects on hearing, sight, intellectual function, diabetes, and other disorders.
- The changes in mitochondrial DNA can have multiple effects.
- Mutation in mitochondrial DNA may or may not be inherited by future generations.
- Genes do not entirely determine a person’s nature. Environmental factors, damage, disease, and freely chosen acts of the organism can interfere with genes’ actual control over what the organism looks like or how it acts. None of this is predictable.
- Germline editing continues to affect future generations, and the effects will tend to be irreversible. The inheritance over just a few generations involves millions of potential variations, mutations, and scenarios that occur as edited genes are inherited. This number of possibilities makes it highly likely that unintended effects will eventually appear in future human beings.
- Biological evolution in the species, whatever the mechanisms for the changes, has caused human beings to become extremely unique and capable animals. Genetic engineering interferes with the natural process of evolution, of which we still have very little understanding as well as extreme differences of opinion and theories.
DNA: The molecules in the body that are naturally inherited from parents and most strongly influence the body’s characteristics, development through life, and many tendencies for behavior. We might say that the “function” of DNA is to pass characteristics from parents to children.
DNA influences the body by interacting in various ways with protein molecules, often “instructing” the way protein is used. Protein is found in every cell of the organism and used to build new cells, repair cells, or create chemicals that affect the organism’s most fundamental processes.
There are four primary substances (bases) in DNA that are organized in long sequences in the shape of strands (chains). Each individual organism’s DNA has a unique pattern of these four bases, although 99% are the same in every person. Human DNA consists of about 3 billion bases, so even a 1% difference can be significant.
DNA creates new copies of itself (replicates) when cells divide. A change in the DNA, called a mutation, can occur very rarely during the replication process.
Nearly all – about 99% – of DNA is called “junk” DNA because it does not provide any instructions (coding) for making or synthesizing proteins. Only recently have scientists figured out that “junk” DNA can be very important to regulating whether genes are turned “on” or “off”.
Gene: A segment of DNA that, as a unified segment, has a particular effect on the organism. Some genes, for example, may cause a human body to have blue eyes, while other genes may influence behavior by causing an organism to have a physical drive to run away when attacked. A single gene can have multiple influences on the body, and most characteristics are generated by a combination of genes.
A single gene may include a few hundred DNA bases up to more than 2,000,000. There may be 25,000 genes in a human being, although this is not known for certain.
Genome: The entire sequence of genes in the DNA of an individual organism. Although every individual organism has a unique genome, scientists often talk about the genome of a species, which is the type and sequence of genes that are nearly identical within all individuals of that species, as well as a description of the genes and their places within DNA that often vary among individuals.
Mitochondria: Mitochondria are structures in cells that breaks down nutrients to produce energy for the cell. They float free throughout the cell and can number in the thousands, although some cells have none. While most DNA is found in the nucleus of a cell, mitochondria have their own ribosomes and DNA. This mitochondrial DNA can be very important in causing problems (“diseases” or “abnormalities”) when the DNA mutates as it is inherited.
RNA: An acid present in the nucleus of all living cells. It carries “instructions” from DNA to control the synthesis of proteins. In some viruses, RNA rather than DNA carries the genetic information.